I am one of many people who have corresponded with Dr. Costantini and I have begun taking his recommended dose of thiamine. I was a little apprehensive, mostly because I didn't know if his success in Italy could be verified. I find these interviews with some of his Italian patients to be convincing.
Dr. Costantini's Patients: I am one of many... - Cure Parkinson's
Please keep us posted on how you do, Jim!
Will do! So far, I am very encouraged, but my symptoms are so subtle that any improvement is even more subtle. I don't want to get carried away, but I'm confident my right arm swings more freely when I walk and my handwriting also seems to have improved, but I've only been on the thiamine for about ten days and I want to be sure any improvement is more than just wishful thinking.
I am in the USA, not Italy. I gladly verify the thiamin having been on it for one year. With outstanding, wonderful results.
Thank you, Roy. I am very new to this site and very new to the world of Parkinson's Disease. This site has been a Godsend, primarily because of smart, caring, experienced people like you. Thank you for sharing your experiences and providing hope and inspiration to people like me.
can it be taken with other natural medicine like siddha. I would like my right hand tremor to stop.
can you suggest the dosage
3g a day. Half in the am, half pm. Watch symptoms closely. If not all, except tremor, not suppressed, raise to 4g day
dr costantini told me 3gm/day. (i am 100#) i am worried about starting the dose too high. do you think it would be ok to start with 2gm and then move up if needed? seems like a safer way to go???
Do you take it injected or orally? Is there a particular brand which is best or just thiamine HCL? What quantity?
2 x day (morning 2g and 5 pm 2g) Vitacost vitamin B1 (as thiamin HCI) 500mg, easy swallow capsules
dr costantini told me to take 3gm/day - 1.5gm at breakfast and 1.5gm at lunch. i wonder why the different times from yours. any thoughts?
Hi there. The dosage is mostly determined by your weight. So if he said 3 g, then I would just stay with that. God bless
Sorry, but the Italian PD is not different if you are not convinced dont try. with respect and friendship Gio
Ha! I totally understand that, but I just wanted to learn about patients not connected to HealthUnlocked who had an even longer history with Dr. Costantini. The interviews help confirm my hope and belief that we aren't all just a herd of buffalo jumping off a cliff because everyone else on HealthUnlocked/Parkinson's Movement is doing it. I'm very hopeful and optimistic, GioCas! I appreciate your leadership regarding Dr. Costantini and thiamine as well!
Well, trying a little , soon you will find out for yourself without anyone telling you anything. I had the same doubts you had, and I say no more. Gio
Again Thiamine is REAL with NO doubt.Even my close friends cannot say if I have PD. I have been taking it for a year and so grateful to have found Dr Costantini.
Best wishes to everyone with PD
today while I was reading Kia's reply my wife called me to do my 250 # thiamine hcl 100ml injection in three years and I'm always better, with the correction of levodopa and some probiotis that I learned to use here on HU. I have a normal life for almost three years and frankly I do not understand all these difficulties in finding the correct dose with the pills because I have always done the injections (with my doctor's recipe) and there are no problems for which I have no doubt even me for three years. I do not have to believe, because I know.. I am lucky.
Gio, Very nice, but the injected dose is only 100mg, which is hundreds of times smaller than 100 ml!
yes little confusion is possible:50mg/ml x 2 in one vial.
Only this they sold !
I take 2 at week.
They are practically 50 mg of b1 dissolved in 50 ml of solution and for each ampoule there are 100 mg of b1 dissolved in 100 ml of solution and corresponds to 1 injection. The eat-potatoes sometimes do so. oppsssssss you will not be one of them. Actually I love the Germans people, they come on holiday to Italy to the campground in Jesolo and they bring the cans of food from home to save money.
Thank you! Further validation of Dr. C and thiamine. We have nothing to lose and everything to gain following his protocol...I am grateful for Dr. C and his medical care for each of us. Thank you, Jim, for this post!
Dr Costantini’s Thiamine protocol is a saviour. NO DOUBT
I emailed Dr. Constantini last week with a short medical history and three short videos to observe my husband's talking, walking and balancing after a sudden pull. The third video didn't show (my bad) how his legs reacted to my pull. Pleasantly surprised, he responded the same day and asked me to repeat the pull/balance video. I redid the video but he couldn't open it (had to save it to his computer and then open it). In any event, I don't know what to think, but I do want my husband to start the B1 protocol. I have found an alternative medicine dr. who was treating his nephew with B1 injections for MS and has managed to stop the progression. This doctor is familiar with the B1 protocol and can give intramuscular injections to my husband. Question is "Shall I wait for Dr. C. response or shall I go ahead with my local doctor and his B1 protocol?
Any suggestions will be greatly appreciated!!
I think it’s totally up to you and your husband, but I think it’s good that you’re giving it a try. Good luck!
Suggesting: Start thiamin HCI , 4g daily, start today. Ref: " I have found an alternative medicine dr. who was treating his nephew with B1 injections for MS and has managed to stop the progression"
Your mention of the doctor who used high dose thiamine for his nephew with MS caught my attention as Dr. Costantini mentioned on the thiamine FAQ page that they had found that thiamine could reduce the fatigue associated with MS. This prompted me to write him right now and ask if he was aware that it could potentially stop disease progression in MS.
He answered already and said that in their initial patients they were only testing for fatigue improvement, but in subsequent patients they found that it helped well beyond just fatigue.
Here is the initial case report that they did a report on for improvement of fatigue :
CASE REPORTHigh dose thiamine improves fatiguein multiple sclerosisAntonio Costantini, Agostino Nappo, Maria Immacolata Pala, Antonietta ZapponeDepartment of NeurologicalRehabilitation, VillaImmacolata, Viterbo, ItalyCorrespondence toDr Antonio Costantini,email@example.comTo cite: Costantini A,Nappo A, Pala MI, et al.BMJ Case Rep Publishedonline: [please include DayMonth Year] doi:10.1136/bcr-2013-009144SUMMARYThe majority of the patients with multiple sclerosis (MS)experience fatigue. Some observations indicate thatfatigue and related manifestations concomitant with MScould be associated with an intracellular mild thiaminedeﬁciency. We recruited 15 patients with MS who alsoexperience fatigue and assessed the severity of thefatigue using the Fatigue Severity Scale. Although bloodthiamine and thiamine pyrophosphate levels were withinnormal limit in all the patients, high-dose thiaminetherapy administered orally or parenterally led to anappreciable improvement of the fatigue. The absence ofapparent decrease in blood thiamine despite thepresence of symptoms referable to a mild thiaminedeﬁciency suggests that these patients may have adysfunction of the mechanisms of intracellular transportor structural enzymatic abnormalities. The admi nistrationof large quantities of thiamine was effect ive in reversingthe fatigue in MS, suggesting that the abnormalities inthiamine-dependent processes could be overcome bydiffusion-mediated transport at supranormal thiamineconcentrations.BACKGROUNDThe basis of this report starts from a previous studyon fatigue in inﬂammatory bowel diseases. Someclinical observations suggesting that fatigue inulcerative colitis (UC) could be the manifestation ofa mild thiamine deﬁciency prompted us to start inJune 2010 a clinical open trial. We treated eightpatients with UC with high-dose oral thiamine andobtained extremely encouraging ﬁndings.1Therefore, we decided to apply the same principlesto chronic fatigue in different autoimmune andinﬂammatory diseases.Fatigue is reported in about 75% of patients withmultiple sclerosis (MS) at some point in the courseof the disease. For many, fatigue is considered to bethe single most debilitating symptom, exceedingpain and even physical disability.2Fatigue alsoimposes signiﬁcant socio-economic consequences,including loss of work hours and in some instances,loss of employment. Nonetheless, fatigue in MSremains poorly understood in its pathogenicmechanisms and often undervalued. No effectivetherapy is available.Fatigue and related disorders (sleep disorders,depression, mood fragility, anxiety, memory loss,attention disorders, lack of tolerance to stress, fre-quent lack of appetite, episodes of tachycardia andextrasistolia, generalised muscular weakness, mus-cular cramps, calf and feet sole pain, temperature-variation intolerance and dry skin) resemble theclinic manifestation of a mild thiamine deﬁciency.3Starting from this similarity, we began to researchthe literature in order to ﬁnd papers concerningdysfunctions of energetic processes in MS.A study on cerebrospinal ﬂuid highlighted that inMS disease progression there is an increase ofextramitochondrial glucose metabolism whichimplicates some sort of mitochondrial dysfunction.4The results of our previous study could be referableto metabolic alterations produced by a thiaminedeﬁciency.1Moreover, several authors haveobserved that mitochondrial injury, resulting inenergy failure, is a key element in MS.5We formulated the hypothesis that the fatiguewas the symptom of a mild thiamine deﬁciencywhich was intrinsic to the MS disease; therefore,we decided to treat the affected patients with highdoses of thiamine.CASE PRESENTATIONFifteen patients, nine women and six men (mean(SD) age: 47.2 (10.0) years), affected exclusively byMS in the remitting phase were selected for thisstudy after obtaining informed consent. Theaverage duration of the disease (SD) was 14.1 (7.5)years. Table 1 shows the demographic informationof the patients. All patients included in this studyfulﬁlled the following criteria:▸ They all had a deﬁnite diagnosis of MS accord-ing to McDonald criteria (2010).▸ None of them presented with cognitiveimpairment.▸ All the patients also showed the other clinicalmanifestations of mild thiamine deﬁciency, suchas sleep disorders, depression, anxiety, moodfragility, memory loss, attention disorders, lackof tolerance to stress, frequent lack of appetite,episodes of tachycardia and extrasistolia, gener-alised muscular weakness, muscular cramps, calfand feet sole pain, temperature-variation intoler-ance and dry skin.▸ All participants were outpatients. Eight patientswere not previously exposed to any medicaltreatment. Five patients were receiving only gla-tiramer acetate (Ga) and two patients, onlyinterferon β during the period of this study. Nopatient had a notorious cause that could lead tochronic fatigue; in all patients, thyroid functionand routine blood tests were within normallimit.For the evaluation of the fatigue the FatigueSeverity Scale (FSS) was employed.6The averagevalue of the FSS was 45.4 before the treatment.Costantini A, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-009144 1Novel treatment (new drug/intervention; established drug/procedure in new situation)
Blood levels of the thiamine and of the thiamine pyrophosphate(TPP) were determined in a core laboratory (Centro DiagnosticoItaliano, Milano, Italy). Vitamin B1level in whole bloodsamples was determined with ClinRep complete kit. In this test,vitamin B1level was quantiﬁed as TPP using high-performanceliquid chromatography (HPLC) with ﬂuorescence detection.Normal values cited in the tables were derived from Lee et al.7The main data of each patient are shown in table 2.High-dose thiamine therapy consisted of 600–1 500 mg/dayorally or 100 mg/mL once a week parenterally. The oral refer-ence doses were retrieved from our previous study on inﬂamma-tory bowel diseases.1We used a dosage calibration according tothe weight of the patients in this way:▸ Patients less than 60 kg → 10 mg/kg/day of thiamine;▸ 60–65 kg → 14 mg/kg/day of thiamine;▸ 65–70 kg → 17 mg/kg/day of thiamine;Table 2 Thiamine, TPP and FSS before and after the therapyPatientThiamine (n.v. 2.1–4.3 mg/L)* TPP (n.v. >49 kg/L)* FSS scoresBefore After Before After Before After1ab7.0 8.4 91.0 48 38 152e6.6 73.1 86.2 65.1 37 183ab6.3 10.8 50.8 119.4 30 144d4.1 7.9 38.8 78.0 51 385d11.4 18.4 89.5 101.7 61 346d8.2 14.4 72.9 40.1 49 407d9.2 14.8 45.2 47.4 55 558e8.4 36.4 105.4 73.2 38 219e7.3 102.7 73.1 72.8 42 1410ac10.8 1414.9 86.4 46.7 21 1211ab5.9 20.6 96.2 69.0 61 4812ab8.0 29.4 122.2 84.1 40 1513d9.4 13.0 106.5 42.8 55 2414e6.1 32.8 73.1 123.5 64 4015ab21.5 22.0 128.1 132.6 39 15average±SD 8.7±3.9 121.3±346.6 84.4±25.3 76.3±29.6 45.4±12.0 26.9±13.8P values by paired t test (two-tailed) 0.24 0.42 <0.0000001*Normal values derived from Lee et al.7TPP, thiamine pyrophosphate; FSS, the Fatigue Severity Scale; a, parenteral administration (the remaining patients were treated orally); b, blood test 2 days after the injection; c, bloodtest 2 h after the injection; d, fasting blood test in the morning; e, blood test 4 h after the intake of the first daily dose; n.v., normal value.Table 1 Demographic information of the patients before therapyPatient Age GenderDiseasedurationMS diseasetherapyBasic ADL BarthelIndex Fatigue-related disorders Symptoms1 46 M 25 Ga 100 Anxiety, muscular cramps, lack of appetite, dry skin Ataxiatetraparesis2 51 F 25 Ga 100 Depression, tachycardia, heat intolerance Ataxia3 38 M 21 Interferon-β 100 Anxiety, sleep disorders, attention disorders Ataxiatetraparesis4 34 F 10 Ga 52 Cold intolerance, lack of tolerance to stress, dry skin paraparesis5 38 M 11 No therapy 19 Anxiety, sleep disorders, memory loss Tetraparesis6 43 F 4 Ga 100 Anxiety, cold intolerance, lack of tolerance to stress Sensitive ataxia7 47 F 13 Ga 100 Anxiety, mood fragility, extrasistolia Ataxia8 37 F 18 Interferon β 100 Anxiety, dry skin, extrasistolia Tetraparesis9 43 F 10 No therapy 100 Anxiety, cold intolerance, dry skin Ataxiatetraparesis10 65 F 13 No therapy 69 Depression, lack of tolerance to stress, dry skin Paraparesis11 44 M 19 No therapy 52 Sleep disorders, lack of tolerance to stress, troubleconcentratingParaparesis12 55 F 3 No therapy 100 Sleep disorders, lack of tolerance to stress, extrasistolia Sensorysymptoms13 48 F 11 No therapy 100 Depression, trouble concentrating, cold intolerance Tetraparesis14 49 M 24 No therapy 100 Anxiety, lack of tolerance to stress, tachycardia Ataxiatetraparesis15 70 M 5 No therapy 52 Anxiety, depression, heat intolerance ParaparesisMS, multiple sclerosis; ADL, activities of daily living; Ga, glatiramer acetate.2 Costantini A, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-009144Novel treatment (new drug/intervention; established drug/procedure in new situation)
▸ 70–75 kg → 20 mg/kg/day of thiamine;▸ 75–80 kg → 23 mg/kg/day of thiamine.In patients more than 80 kg, parenteral administration wasperformed due to the patient’s reluctance to take large amountof pills. We considered the score of the FSS as follows:▸ Up to 9 points → no fatigue;▸ More than 9, up to 36 points → medium-low fatigue (twocases);▸ More than 36 points → severe fatigue (13 cases).6Every 3 days, the patients were contacted in order to trackthe course of the treatment.OUTC OME AND F OLLOW-UPThe evaluation of the fatigue using the FSS scale was repeated20 days after the beginning of the therapy. A partial regressionof the fatigue was shown in 14 patients out of 15 (except forpatient 7) (93.3% of the cases) (table 2). A detailed observationrevealed that improvement of fatigue was obtained within hoursfrom the ﬁrst parenteral administration or within 2–3 days afterthe beginning of the oral therapy. The average value of the FSSbefore the therapy was 45.4 while the average value of the FSSafter the therapy was 26.8, showing a statistically signiﬁcantimprovement by 41% ( paired t test, p<0.0001, table 2). Thepatients moreover reported an almost complete disappearanceof fatigue-related symptoms such as an improvement of theintolerance to heat variations, sleep disorders, depression,anxiety, irritability, dry skin, lower leg swelling and tachycardia.Motor and other neurological symptoms did not show an appre-ciable clinical improvement.During this study, we have never recorded any side effect.8Arecent check-up (after 18 months of treatment) did not showany decrease of the efﬁcacy of the therapy.DISCUSSIONThis pilot study showed that treatment with high doses of thia-mine was associated to a remarkable improvement offatigue-related symptoms in MS, which closely resemble a mildthiamine deﬁciency.910During this study we have neverrecorded any side effect.The presence of manifestations of a mild thiamine deﬁciencyeven in patients with normal concentrations of thiamine andTPP in the blood could be explained if referred to a form ofthiamine deﬁciency due to a dysfunction of the vitamin B1active intracellular transport, or to structural enzymatic abnor-malities.911We deem that the concentration of thiamine in theblood before and after the therapy has higher relevance inunderstanding the action of vitamin B1in these cases because, itis known that thiamine is converted into TPP within the cellsand thus, TPP concentration in the blood may not be related toimprovement of the diffusion mechanism throughout the organ-ism.12On the other hand, the much higher content of thiaminein the blood after the high-dose therapy leads to an incrementof the intracellular TPP and to an improvement of the manifes-tations as shown in our observations. In the 1950s and 1960 s,several authors treated MS using TPP without any result.13Wedeem that if the aforementioned early studies focused on admin-istration of thiamine rather than TPP, they might have witnessedan improvement of the fatigue due to the action of thiamine atcellular level in favouring the production of TPP.Unfortunately, for the current study we were not in the pos-ition to measure the TPP levels in the cells. However, whateverbe the kind of dysfunction taking place in our patients, thesymptoms were responsive to administration of large quantitiesof thiamine. The administration of large quantities of thiamineorally or parenterally increases its concentration in the blood tothe levels which the passive transport restores the normalglucose metabolism. According to literature, the dysfunction ofactive intracellular transport or enzymatic abnormalities couldbe overcome by diffusion mediated at supranormal thiamineconcentrations.911Other mechanisms have been thought to beresponsible of the efﬁcacy of high doses of thiamine, but wereckon these are less likely.11The doses employed in this study were calculated empiricallybased on previous studies on inﬂammatory bowel diseases andthey may be deﬁned with higher accuracy as a result of furtherstudies, in order to improve the efﬁciency of the therapy.As of today, there is only one non-alcoholic case report ofWernicke’s encephalopathy manifesting with symptoms of thia-mine deﬁciency with normal blood concentrations of thiaminelevel, caused by vomiting and severe diarrhoea secondary toClostridium difﬁcile colitis.14Clinical improvements are docu-mented following administration of pharmacological doses ofthiamine in patients with inborn errors of metabolism such asthiamine-responsive megaloblastic anaemia and Wernicke’s likeencephalopathy.911In addition, recently, improvement of fatigue with high dosesof thiamine was observed in a case of Spinocerebellar Ataxiatype 2.15In conclusion, the current pilot study demonstrated the pos-sible effectiveness of high-dose thiamine therapy in fatigue ofpatients with MS. In order to conﬁrm our observations,placebo-controlled randomised trials and further studies enableto explain the exact pathogenesis of intracellular thiamine deﬁ-ciency are warranted.Learning points▸ The treatment described in this paper, that is, high-dosethiamine supplementation in patients with multiple sclerosisand fatigue, is immediately available.▸ In literature there is no study that has observed side effectslinked to daily use of high doses of thiamine.▸ We believe that this report opens a ray of hope for thetherapy of chronic fatigue.Acknowledgements The authors thank Marco Colangeli, Father Emilio Blasi,Emmanuel Nabaloum, the personnel of the Department of Neurologic Rehabilitationof the Clinic ‘Villa Immacolata’ of Viterbo, Maria Pia De Santis, Umberto Morgia,Pina Paolella, MD, and Prof. Aldo Laterza (authors’ Former Neurology Professor), fortheir outstanding support and encouragement.Contributors AC and AN were involved in conception and design, acquisition ofdata, analysis and interpretation of data, drafting, critical revision, supervision of themanuscript. MIP and ZA were involved in acquisition of data, drafting,administrative, technical and material support.Competing interests None.Patient consent Obtained.Provenance and peer review Not commissioned; externally peer reviewed.REFERENCES1 Costantini A, Pala MI. Thiamine and fatigue in inﬂammatory bowel diseases: anopen-label pilot study. J Altern Complement Med. Published Online First: 4 Feb2013. doi:10.1089/acm.2011.08402 Braley TJ, Chervin RD. Fatigue in multiple sclerosis: mechanisms, evaluation andtreatment. Sleep 2010;33:1061–7.Costantini A, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-009144 3Novel treatment (new drug/intervention; established drug/procedure in new situation)
3 World Health Organization. Thiamine deﬁciency and its prevention and control inmajor emergencies. Geneva: Department of Nutrition for Heath and Development,WHO; 1999, Report no: WHO/NHD/99. 13.4 Regenold WT, Phatak P, Makley MJ, et al. Cerebrospinal ﬂuid evidence of increasedextra-mitochondrial glucose metabolism implicates mitochondrial dysfunction inmultiple sclerosis disease progression. J Neurol Sci 2008;275:106–12.5 Mahad D, Lassmann H, Turnbull D. Mitochondria and disease progression inmultiple sclerosis. Review Neuropathol Appl Neurobiol 2008;34:577–89.6 Krupp LB, LaRocca NG, Muir-Nash J, et al. The fatigue severity scale. Application topatients with multiple sclerosis and syst emic lupus erythema tosus. Ar ch Neurol1989;46:1121–3.7 Lee BL, Ong HY, Ong CN. Determina tion of thiamin e and its phosphate esters bygradient-elution high-performance liquid chroma togr aphy . J Chr oma togr 1991;567:71–80 .8 Smithline HA, Donnino M, Greenblatt DJ. Pharmacokinetics of high-dose oralthiamine hydrochloride in healthy subjects. BMC Clin Pharmacol 2012;12:4.9 Lonsdale D. A review of the biochemistry, metabolism and clinical beneﬁts ofthiamin(e) and its derivatives. Evid Based Complement Alternat Med 2006;3:49–59.10 Fauci S, Braunwald E, Kasper DL, et al. Harrison ‘s principles of internal medicine17th edn., New York: McGraw-Hill, Inc., 1999.11 Kono S, Miyajima H, Yoshida K, et al. Mutation in a thiamine-transporter gene andWernicke’s-like encephalopathy. N Engl J Med 2009;360:1792–4.12 Song Q, Singleton CK. [Mitochondria from cultured cells derived from normal andthiamine-responsive megaloblastic anemia individuals efﬁciently import thiamine
Excellent! Guess my alternative medicine doctor is a good one.
He ordered the B1 vials more than a week ago, but he hasn't received them yet. I was really surprised when he told me that he knew of the Thiamine CHL wonders and that he had used it on his sister's son. He had stopped the progression, but sister wanted to completely reverse her son's MS, so she decided to stop the B1 protocol and turned to conventional medicine approach. Her son is now on a wheel chair when he was on his two feet while on B1 protocol.
i contacted dr costantini, and he responded the same day (which surprised me). he asked me for my ht & wt, etc. but now its been 4 days. i dont want to email him again and be pushy, but i am anxious to hear back from him. how long did you have to wait to get a reply? thanks in advance.
I gave him my height, weight, symptoms, and diagnosis date in my first email, but if I were you, I’d follow up again. I wouldn’t worry about being pushy. A lot is at stake...
Doc Costantini is kind and will understand as "A lot is at stake..."
royprop - dr costantini responded and recommended 3gm/day. (my wt is 100#) but i am nervous about feeling worse if the dose is too high. when you increased your dose, how long did it take for you to notice that your symptoms were worsening? and how long did that last before returning to the previous state? do you think it would matter if i started out at 2gm and then went up to 3gm if i needed to. that makes more sense to me.
I emailed Dr. June 4 and he responded later that day and recommended 3/500mg pills 1 time in morning and 1 time at lunch. Tried for 4 days and I felt very anxious and some nausea so emailed again and he responded "halve the dose".
So far not any change. I'll update again soon
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